AB0031 ASSOCIATION BETWEEN OMEGA-3/6 FATTY ACIDS AND OSTEOARTHRITIS: A TWO-SAMPLE MENDELIAN RANDOMIZATION STUDY
Authors: S. Wei, Y. Lu, S. Song, J. Qiao, S. X. Zhang, X. Li
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Osteoarthritis (OA) is the most common degenerative joint disorder worldwide. Accumulating evidence has demonstrated the associations of omega-3 and omega-6 PUFAs with the disease activity and inflammatory mediators of OA, omega-3 polyunsaturated fatty acids (PUFAs) are recognized for their anti-inflammatory properties<sup>[1]</sup>, while omega-6 FAs are inflammatory mediators that are increased in joints with OA<sup>[2]</sup>. However, the evidence of causal links of omega-3 and omega-6 PUFAs on the risk for OA remains inconclusive. <h3>Objectives</h3> This study was conducted to evaluate the causal relationships between omega-3/6 and OA by performing the two-sample Mendelian randomization (MR) analysis. <h3>Methods</h3> The data set of this study was from the publicly available genome-wide association study (GWAS). The genetic instrumental variables for omega-3/6 were derived from the UK Biobank (UKB) and included 114,999 participants. Summary statistic data for OA originated from a meta-analysis of GWAS with an overall 50 508 subjects of European ancestry. In the MR Approach, the IV analysis is based on three strict assumptions, namely that IV should be strongly correlated with exposure, independent of confounding factors associated with direction and outcome, and influence outcome solely through exposure. We screened SNPs with genome-wide significance (P &lt; 5 × 10<sup>–8</sup>). To ensuring that the SNPs were valid and independent, we removed the linkage disequilibrium (LD) between the SNPs at r<sup>2</sup> &lt; 0.001, and &lt;10,000 kb in size. Furthermore, the secondary phenotype of each SNP was retrieved to ensure that it was not associated with OA. The F statistic &gt; 10 indicated a relatively strong estimated effect of IVs. Subsequently, two-sample Mendelian randomization analyses were conducted with inverse variance weighted (IVW), MR-Egger regression and weighted median methods. Sensitivity analyses were then conducted to assess the robustness of our results. <h3>Results</h3> The inverse-variance weighted (IVW) method revealed that higher omega-6 levels were correlated inversely with the risk of OA (β = -0.08, 95% CI [-0.16 to -0.02], P = 0.01), but no causal effect of omega-3 on the risk OA was observed (β = -0.04, 95% CI [-0.10 to -0.02], P = 0.15). The causal estimates from MR-Egger and weighted median methods revealed completely concurring effect directions (β＜0, p＜0.05). Cochran’s Q of IVW analysis showed that there was heterogeneity among SNPs (P＜0.05), it does not affect the results of IVW, which shown the reliability of our results. MR-Egger regression analysis demonstrated that SNPs could have no-horizontal pleiotropy between omega-6 fatty acids and risk of OA (P＞0.05). Moreover, Results of the leave-one-out method suggested that MR results were not influenced by individual SNPs. <h3>Conclusion</h3> This study revealed that the high level of omega-6 predicted by genes can reduce the risk of OA. This implies that supplementing omega-6 fatty acids in our diet may be a potential nutritional modality for the prevention of OA. <h3>References</h3> [1]P Wang, K Xiang, YY Xu, et al. Genetically Predicted Circulating Omega-3 Fatty Acids Levels Are Causally Associated With Increased Risk for Systemic Lupus Erythematosus. <i>Front Nutr</i> 2022;9:783338. [2]AM Valdes, S Ravipati, P Pousinis, et al. Omega-6 oxylipins generated by soluble epoxide hydrolase are associated with knee osteoarthritis. <i>J Lipid Res</i> 2018;59(9):1763-70. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.